Erdheim-Chester Disease Presenting Research Articles

Erdheim–Chester disease presenting with eruptive fibrous histiocytomas

AbstractErdheim–Chester disease (ECD) is a rare, non‐Langerhans histiocytic disease, with the manifestation of cutaneous lesions becoming further recognised and understood. Most commonly presenting with xanthelasma‐like lesions, cutaneous manifestations are the first noticeable sign of ECD in a significant number of patients. Other commonly reported cutaneous lesions of ECD include panniculitis‐like lesions and granuloma annulare‐like lesions. While previously reported papular lesions of ECD include crusty yellow and erythematous papules, small, pink to fleshy coloured papules, and verruca plana‐like papules, papulonodular eruptions consistent with fibrous histiocytomas are a rare and underreported sequala of ECD. Here, we report an 86‐year‐old male with a history of prostate and bladder cancer who presented with eruptive fibrous histiocytomas, prompting workup that lead to a diagnosis of ECD. The patient received expedited imaging given the rare association of eruptive fibrohistiocytic lesions with malignancy, revealing diffuse perinephric and urothelial soft tissue thickening and enhancement, which was biopsied and found to harbour the BRAF V600E mutation. One could reasonably hypothesise that the pathologic mechanism occurring in the perinephric and urothelial soft tissue areas of this patient bodes similarities to the cutaneous sites consistent with the fibrohistiocytic lesions. This may present a potential clue to the poorly understood origin and pathogenesis of ECD.

Erdheim-Chester Disease Presenting as Bilateral Facial Masses

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis with unknown etiology. It is recently recognized to be neoplastic with genetic mutations affecting the mitogen-activating protein kinase (MAPK) pathway. We here present a case of a 49-year-old female who initially presented in 2012 with bilateral facial masses to a tertiary care center. These were removed but later recurred over a period of ten years. She then presented with xanthelasmas, bone lesions, secondary infertility due to hypothalamic hypogonadism, diabetes insipidus, and Hashimoto’s hypothyroidism. The facial masses were biopsied, and they showed classic morphological features in the form of diffuse infiltration by foamy histiocytes, with scattered Touton type of giant cells, patchy lymphocytic infiltrates, and dense fibrosis. The presented ECD case is particularly interesting due to the recurrent bilateral facial masses. To the best of our knowledge, this is the first documented case in Oman. The patient is stable and is being followed up in the clinic.
 Keywords: Erdheim-Chester disease, Langerhans cell histiocytosis.

P056 Rheumatology haematology interface: an unusual case of aortitis

Abstract Background/Aims In rheumatological practice it in not unusual to see patients with haematological involvement. We would like to present a very rare diagnosis of Erdheim-Chester disease presenting as retroperitoneal fibrosis and large vessel vasculitis who failed to respond to conventional treatments with steroids and methotrexate. Methods A 71-year-old man presented to haematology with retroperitoneal mass. This was investigated with CT thorax, abdomen and pelvis and a biopsy was performed which was negative for haematological malignancies. However, CT scan picked up thickening of aorta and a PET scan was performed subsequently confirming widespread aortitis and peri-renal mass thought to be consistent with retroperitoneal fibrosis. The patient was started on reducing course of oral steroids with a working diagnosis of retroperitoneal fibrosis with large vessel vasculitis. Results Subsequent staining for IGG-4 was negative and biopsy was not typical with IgG4 cells. The patient was started on high doses of oral steroids by haematologist with Methotrexate started subsequently by rheumatologist due to persistent changes on PET scan, high inflammatory markers and worsening of patient with generalised malaise, weight loss and fatigue. The patient failed to respond to uptitrated doses of methotrexate and was discussed with a specialist unit for consideration of anti-IL6 tocilizumab to control his large vessel vasculitis. On discussion of imaging in MDT, unusual appearance with sparing of ureters, splaying of peri-nephric fat, lack of IgG4 cells pointed towards an alternative diagnosis. Conclusion The patient was subsequently discussed in the national adult histiocytosis meeting with national and international haematologists. The clinical presentation, radiological appearance was thought to be classic of Erdheim-Chester disease, a rare form of adult onset histiocytosis. After further discussions with specialist centre the patient has been commenced on trametinib, a MEK inhibitor treatment (cell tissue negative for BRAF mutation). The patient has recently developed heart failure and has undergone right heart catheter which has found extremely rare pulmonary artery vasculitis too. Disclosure S. Raghuvanshi: None. B. Tarar: None. A. Shaaban: None.

Erdheim–Chester disease presenting as an intracardiac mass and pericardial effusion confirmed by biopsy: a case report

BackgroundErdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that can affect the bones, heart, lungs, brain, and other organs. Cardiovascular involvement is common in ECD and is associated with a poor prognosis. Here, we report a case of ECD presenting as an intracardiac mass and pericardial effusion confirmed by biopsy with sternotomy.Case summaryA 54-year-old man was admitted because of dyspnoea. He was previously diagnosed with bilateral hydronephrosis and retroperitoneal fibrosis. Echocardiography revealed a large amount of pericardial effusion and echogenic mass on the right atrial (RA) side and atrioventricular (AV) groove. Cardiac magnetic resonance imaging and positron emission tomography-computed tomography (CT) revealed infiltrative mass-like lesions in the RA and AV groove. Pericardial window formation and pericardial biopsy were performed, and the pathologic results showed only pericardial fibrosis with no specific findings. Bone scan revealed increased uptake in the long bones. Considering the high probability of ECD based on the patient’s manifestations and the imaging findings, we performed a cardiac biopsy with median sternotomy despite initial insufficient pathologic results in the pericardial biopsy. The surgical findings included multiple irregular and firm masses on the cardiac wall and large vessels; after obtaining a large amount of suspicious mass, ECD accompanied with CD68 (+) and BRAF V600E mutation was confirmed.DiscussionErdheim–Chester disease can be associated with various forms of cardiovascular involvement. Considering the multi-systemic manifestations and difficulty in identifying this rare disease, a comprehensive and meticulous diagnostic work-up is crucial.

Erdheim-Chester disease presenting as acute ischaemic cardiomyopathy and aortitis in a BRAF V600E-negative patient.

Erdheim-Chester disease presenting as acute ischaemic cardiomyopathy and aortitis in a BRAF V600E-negative patient.

Isolated thoracic intramedullary Erdheim-Chester disease presenting with paraplegia: a case report and literature review

BackgroundErdheim-Chester disease (ECD) is a rare, idiopathic, systemic non-Langerhans cell histiocytosis involving long bone and visceral organs. Central nervous system (CNS) involvement is uncommon and most cases develop as a part of systemic disease. We present a rare case of variant ECD as an isolated intramedullary tumor.Case presentationA 75-year-old female patient with a medical history of diabetes and hypertension presented with sudden-onset flaccid paraparesis for 1 day. Neurological examination revealed grade 2–3 weakness in both legs, decreased deep tendon reflex, loss of anal tone, and numbness below T4. Leg weakness deteriorated to G1 before surgery. Preoperative magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed an intramedullary mass lesion at T2-T4 with no systemic lesion, which was heterogeneous enhancement pattern with cord swelling and edema from C7 to T6. Gross total removal was achieved for the white-gray-colored and soft-natured intramedullary mass lesion with an ill-defined boundary. Histological finding revealed benign histiocytic proliferation with foamy histiocytes and uniform nuclei. We concluded it as an isolated intramedullary ECD. The patient showed self-standing and walkable at 18-month with no evidence of recurrence and new lesion on spine MRI and whole-body FDG-PET/CT until sudden occurrence of unknown originated thoracic cord infarction.ConclusionsWe experienced an extremely rare case of isolated intramedullary ECD, which was controlled by surgical resection with no adjuvant therapy. Histological examination is the most important for final diagnosis, and careful serial follow-up after surgical resection is required to identify the recurrence and progression to systemic disease.

Teaching Video NeuroImages: Multisystemic Erdheim-Chester Disease Presenting as a Cerebellar Ataxia.

A 41-year-old man was admitted to the neurology ward due to progressive vertigo and unsteadiness for the previous 2 months. Neurologic examination was remarkable for a global cerebellar syndrome. Investigation with brain MRI led to the hypothesis of a histiocytosis due to infiltrative lesions of the pons, cerebellar peduncles, and pituitary. Therefore, investigation progressed with chest/abdomen/pelvis CT, bone scintigraphy, and a tibial biopsy that confirmed the diagnosis of Erdheim-Chester disease (figures 1 and 2, video).

Case of BRAF mutant Erdheim-Chester disease presenting with multisystem involvement: A case report

Objective: Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis of unknown etiology. It is a multisystemic disease that can involve bones, skin, brain, retroperitoneum, cardiovascular system, endocrine system, and lungs. Diagnosis is made by clinical findings, imaging results, and histopathological examination. BRAFV600E (B-rapidly accelerated fibrosarcoma gene) mutation is found in more than half of the cases. When Erdheim-Chester disease is not considered the differential diagnosis, it is not possible to diagnose and treat. In this case report, an Erdheim-Chester case with symptomatic, multisystem involvement, BRAFV600E mutation, and initiated vemurafenib treatment is presented in the light of literature data.

Erdheim Chester disease presenting as sclerosing mesenteritis

Erdheim Chester disease presenting as sclerosing mesenteritis

A rare case of non-Langerhans cell histiocytosis/ Erdheim-Chester disease presenting as desquamative gingivitis and oral mucosal erythema

Background Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by BRAFV600 E mutations in greater than 50% of patients; multisystemic involvement, such as skin (xanthelasma); heart (pericardial effusion); central nervous system (brain-stem lesions); and bone lesions. ECD has a distinct histopathology and immunochemistry profile, which is negative for CD1 a, S100, and Langerin. Craniofacial involvement has been reported in less than 10 cases and described as multiple, solitary, well-defined radiopaque/lucent lesions of the jaws. We report a case of ECD, which initially included desquamative gingivitis, mucosal erythema, and edema. Case Summary A 62-year-old white woman was referred by her local dentist to the Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, in December 2017, with the chief complaint of mouth sensitivity. Her medical history was notable for a 7-year history of intermittent bone pain, nonpruritic, erythematous, papular rashes of the neck, extremities, and trunk, as well as gingival erythema. She was diagnosed with ECD by a hematologist–oncologist in December 2010 based, in part, on tibial biopsy and the presence of BRAFV600 E mutation. Her medications included prednisone 40 mg 4 times daily by mouth, Bactrim 4 times daily by mouth, subcutaneous MTX 27.5 mg weekly injection, and dabrafenib 150 mg every 12 hours. She reported having a 10-year history of intermittent sensitivity, redness, and swelling of the gingiva, without any known triggers or patterns. On oral examination, there was diffuse desquamation, erythema, and edema of the buccal and palatal gingivae, as well as erythema of the mid–hard palatal mucosa. Differential diagnoses were ECD, vesiculobullous disorders, and vasculitis. With the patient's consent, an incisional biopsy specimen was obtained, and histopathology revealed the presence of chronic inflammation and a scant histiocytic infiltrate. The patient was managed with topical clobetasol 0.05% via custom trays to the maxilla and the mandible; the patient reported a greater than 75% improvement in sensitivity score after 1 month of use. Five months later, she presented with 2 erythematous nodules (#12 and #19), which were consistent with pyogenic granulomas on excisional biopsy. Conclusions This is the first report of potential oral mucosal involvement of ECD, with the noted desquamative gingivitis and erythema as its oral presentation.

RETRACTED: Erdheim-Chester disease presenting as cardiac tamponade: features on multimodal imaging.

RETRACTED: Erdheim-Chester disease presenting as cardiac tamponade: features on multimodal imaging.

Erdheim-Chester Disease Presenting as an Anterior Mediastinal Tumor without Skeletal Involvement

Erdheim-Chester disease (ECD) is a form of non–Langerhans cell histiocytosis that most commonly involves the skeletal system. We report an unusual case of ECD presenting as an anterior mediastinal tumor without skeletal involvement. A 60-year-old man with no remarkable medical history was referred for evaluation of a mediastinal mass. The patient underwent surgical excision of the tumor via video-assisted thoracoscopic surgery. Histologic examination revealed marked proliferation of atypical histiocytes with sclerosis, and the results of immunohistochemical staining were suggestive of ECD.

Erdheim-chester disease presenting with hypopituitarism and diabetes insipidus

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Erdheim-Chester Disease Presenting as Abdominal Pain

Erdheim-Chester Disease (ECD) is an abnormal malignant proliferation of histiocytes that can affect many systems, most commonly the bone. This is a rare disease with few reported cases and is characterized by an infiltration of foamy histiocytes. Although ECD is classified as an orphan disease, those in the field of gastroenterology should be aware of this disorder because of its ability to produce multisystem symptoms, most notably vague abdominal pain with a similar presentation as gastroesophageal reflux disease (GERD). A 63-year-old male with a past medical history of osteoarthritis, GERD, and myocardial infarction (MI) presented with upper abdominal pain for several months duration, worse with palpation. Patient had lower and upper endoscopy revealing only mild gastritis. Abdominal pain was not relieved by a 30-day trial of pantoprazole. Abdominal and pelvic CT showed abnormal thickening around the kidneys, adrenals, and descending aorta (Image 1). This radiographic image displayed a characteristic “hairy kidney” appearance associated with ECD. Further assesment included a follow up bone scan revealing active regions of uptake in the bilateral distal femurs and bilateral distal tibias (Image 1). The retroperitoneal mass was biopsied for evaluation. Histopathologic findings included lymphocytic infiltrate with foamy cytoplasm, irregular nuclei, and rare Touton type giant cells. These cells stained positive for CD68 and negative for S100 (Image 2). This was all consistent with a diagnosis of ECD. Cells were tested for a BRAF V600 E mutation, but results of this test were inconclusive. Because of the mild symptoms the patient was not started on any chemotherapy for his condition. At one year follow up, the patient developed radiating back pain and diabetes insipidus. Despite worsening symptoms, the mass burden appears to be stable. It is estimated that up to 68% of ECD cases occur with renal and retroperitoneal involvement. Therefore, it is possible for a patient with ECD to present to a gastroenterologist complaining of vague abdominal pain. In this case, the patient's abdominal pain was palpable and not relived with PPI treatment, thus warranting further investigation with CT. Catching ECD early is of particular importance because approximately 54% of ECD cases are positive for the BRAF mutation and can be treated with BRAF inhibitors such as vermurafenib.FigureFigure

Erdheim-Chester Disease Presenting as a Solid Renal Mass

Erdheim-Chester disease is a rare, systemic histiocytic disorder, usually presenting due to bone manifestations. The most commonly seen urologic manifestation is retroperitoneal fibrosis, leading to ureteral obstruction. We describe a patient with a solid right renal mass, initially concerning for renal cell carcinoma, in addition to diffuse retroperitoneal fibrosis and a chronically obstructed left kidney. The renal mass and retroperitoneal fibrosis are thought to be caused by Erdheim-Chester disease based on imaging findings and biopsy results.

Erdheim chester disease presenting as bone pain with a lytic lesion: Case history and review of the literature

Erdheim Chester Disease (ECD) is characterized by organ infiltration by CD68 positive and CD1a negative non-LangerhansHistiocytes. The presentation of ECD can vary from bone pain due to bone infiltration to multi-systemic forms involving thecardiovascular system. The prognosis of ECD is poor; however, with increased understanding of the pathogenesis, this has led tothe evolution of new therapeutic strategies. Because of the increased need for understanding this disease we present a case of a man, who presented to us with bone painand radiographs showing a lytic lesion in his left femur. Upon further investigation with magnetic resonance (MR) imaging andtechnetium 99 m bone scan we chose to undergo an open biopsy, which led to the definitive diagnosis. We outline the currenttreatment regimen and its evolution as our understanding of the pathogenesis of ECD has increased.

Rare form of erdheim-chester disease presenting with isolated central skeletal lesions treated with a combination of alfa-interferon and zoledronic Acid.

Erdheim-Chester disease (ECD) represents a clonal non-Langerhans histiocytosis, which manifests under an extensive variety of clinical symptoms. This creates a challenge for the physician, who is required to recognize and diagnose the disease in the early stages. Despite this considerable challenge, in the last decade there has been a dramatic increase in ECD diagnoses, in most part due to an increasing awareness of this rare disorder. Involvement of the axial skeleton is exclusively uncommon with no official recommendations for the treatment of the bone lesions. Here, we present a case report of a young male patient with isolated lesions of the spine, ribs, and pelvis, who was successfully treated with a combination therapy of alfa-interferon and zoledronic acid.

Erdheim–Chester disease presenting with an intramedullary spinal cord lesion

Erdheim–Chester disease (ECD) is a rare form of nonLangerhans histiocytosis characterized by multi-systemic xanthogranulomatous infiltration. The disease commonly affects the skeleton, but may also involve the skin, viscera including the cardiovascular system and lungs, as well as the central nervous system [1–4]. Diagnosis is based on histopathology typically showing infiltration by histiocytes expressing CD68, but not CD1a [3]. In the nervous system, ECD commonly affects the neurohypophysis resulting in diabetes insipidus. Extrahypophyseal nervous system involvement is seen in about a third of ECD patients and includes intra-axial infiltrative lesions, meningioma-like masses, and periarterial infiltration [3, 5, 6]. Spinal cord involvement may occur due to extramedullary masses [3, 7, 8] but intra-axial cord lesions are rare and only a single patient has been described [9]. We report a case of ECD presenting with progressive spastic paraparesis caused by an intramedullary cord tumor. A 31-year-old female was referred to our clinic with a 10-year history of slowly progressive gait difficulties due to a spinal cord mass. She also complained of polydipsia, polyuria, and irregular menstruation. Clinical examination revealed spastic paraparesis with extensor plantar responses and normal sensory function. There was saccadic smooth pursuit in all directions and horizontal nystagmus on lateral gaze, but no other signs of cerebellar dysfunction. She had multiple periorbital xanthelasma-like lesions (Fig. 1). She did not complain of skeletal pain. MRI of the brain revealed symmetrical high T2 signal in the cerebellar white matter, sparing the dentate nuclei. There was calcification of the dentates and globus pallidus (Fig. 1). MRI of the spine showed diffuse, non-contrast enhancing, low T1 and T2 signal changes in multiple cervical and thoracic vertebrae. There was a fusiform masslesion of the thoracic cord showing inhomogeneously high T2 signal intensity and partial contrast enhancement (Fig. 2). Scintigraphy with technetium 99 and fluorodeoxyglucose positron-emission tomography (FDG-PET) showed pathological tracer uptake in the epiphyses of long bones, several cervical and thoracic vertebra (corresponding to signal changes on the MRI) and parts of the facial skeleton. Skeleton radiograms showed moderate hyperostosis of the skull and sclerotic changes in the epiphyses of the long bones (Fig. 1). A computed tomography (CT)-guided biopsy of the 9th thoracic vertebra was performed. Histology revealed a hypercellular bone marrow with focal fibrosis and infiltration C. Tzoulis (&) I. O. Gjerde Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway e-mail: chtzoulis@yahoo.com; charalampos.tzoulis@helsebergen.no

Cytomorphology of Erdheim–Chester disease presenting as a retroperitoneal soft tissue lesion

Erdheim–Chester disease (ECD) is a rare, multisystem disorder of macrophages. Patients manifest with histiocytic infiltrates that lead to xanthogranulomatous lesions in multiple organ systems. The cytologic features of this disorder are not well characterized. As a result, the cytologic diagnosis of ECD can be very challenging. The aim of this report is to describe the cytomorphology of ECD in a patient presenting with a retroperitoneal soft tissue lesion. A 54-year-old woman with proptosis and diabetes insipidus was found on imaging studies to have multiple intracranial lesions, sclerosis of both femurs and a retroperitoneal soft tissue mass. Fine needle aspiration (FNA) and a concomitant core biopsy of this abnormal retroperitoneal soft tissue revealed foamy, epithelioid and multinucleated histiocytes associated with fibrosis. The histiocytes were immunoreactive for CD68, CD163, Factor XIIIa and fascin, and negative for S100, confirming the diagnosis of ECD. ECD requires a morphologic diagnosis that fits with the appropriate clinical context. This case describes the cytomorphologic features of ECD and highlights the role of cytology in helping reach a diagnosis of this rare disorder.

Erdheim Chester disease presenting as slowly progressive cerebellar syndrome and asymptomatic widespread skeletal involvement

Erdheim Chester disease presenting as slowly progressive cerebellar syndrome and asymptomatic widespread skeletal involvement